ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Pediatric Gastroenterology, Hepatology and Nutrition
Isolated Ventricular Septal Defect Is Not a Risk Factor for Celiac Disease: Evidence From a Large Real-World Data Cohort of 493,382 Children
Provisionally accepted
Ramon Cohen1Haitham Abu Khadija1Shay Nemet1Mohammad Masu'd1Duha Najajra1
Alena Kirzhner1
Tal Schiller2
Nizar Abu Hamdeh1Shira Bezalel-Rosenberg1Ilan Asher1Ali Abdallah1Keren Mahlab-Guri1
Mohammad Alnees1*Daniel Elbirt1- 1Kaplan Medical Center, Rehovot, Israel
- 2Tel Aviv University Faculty of Medical and Health Sciences, Tel Aviv-Yafo, Israel
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Abstract Background: Ventricular septal defect (VSD) is one of the most common congenital heart defects in children. Celiac disease (CD) clusters with autoimmune conditions and chromosomal syndromes, but it is unclear whether isolated VSD is independently associated with CD. Methods: We performed a population-based retrospective cohort study using Clalit Health Services electronic records. Children aged 0–10 years were followed for up to 10 years for incident CD. Multivariable Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 97.5% confidence intervals (CI) for the association between VSD and CD, adjusting for age, sex, type 1 diabetes mellitus, autoimmune disease, immunodeficiency, and chromosomal anomalies. Results: The Cox model included 493,382 children. VSD was not independently associated with an increased risk of CD (HR 1.25, 97.5% CI 0.85–1.82). In contrast, established comorbidities showed strong associations with CD: type 1 diabetes mellitus (HR 10.26, 97.5% CI 8.15–12.91), chromosomal anomalies (HR 5.20, 97.5% CI 3.67–7.37), and autoimmune diseases (HR 2.07, 97.5% CI 1.39–3.10). Conclusion: In this large real-world data, isolated VSD was not an independent risk factor for CD, whereas type 1 diabetes mellitus, chromosomal anomalies, and autoimmune diseases were strongly associated with CD. These findings do not support routine CD screening based solely on VSD status in children.
Keywords: Autoimmune Diseases, Celiac Disease, Chromosomal abnormalities, congenital heart disease, Epidemiology, Pediatrics, type 1 diabetes mellitus, Ventricular septal defect
Received: 21 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Cohen, Abu Khadija, Nemet, Masu'd, Najajra, Kirzhner, Schiller, Abu Hamdeh, Bezalel-Rosenberg, Asher, Abdallah, Mahlab-Guri, Alnees and Elbirt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mohammad Alnees
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